Infliximab and the risk of latent viruses reactivation in active Crohn's disease

• Published in: Inflammatory bowel diseases Vol. 13; no. 7; pp. 896 - 902
• Main Authors: Lavagna, Alessandro, Bergallo, Massimiliano, Daperno, Marco, Sostegni, Raffaello, Costa, Cristina, Leto, Rosalia, Crocellà, Lucia, Molinaro, Giancarlo, Rocca, Rodolfo, Cavallo, Rossana, Pera, Angelo
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2007
• Subjects: Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Viral - blood; Betaherpesvirinae - isolation & purification; Crohn Disease - drug therapy; Crohn Disease - virology; Crohn's disease; Cytomegalovirus; DNA, Viral - blood; EBV; Epstein-Barr virus; Gastrointestinal Agents - adverse effects; Gastrointestinal Agents - therapeutic use; Herpesvirus 4, Human - isolation & purification; Herpesvirus 8, Human - isolation & purification; HHV‐6; HHV‐7; HHV‐8; Human cytomegalovirus; human herpes virus‐6; human herpes virus‐7; human herpes virus‐8; Human herpesvirus 6; Humans; Infliximab; JC Virus - isolation & purification; JCV; JC‐polyomavirus; lymphoma; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Virus Activation - drug effects; Virus Latency - drug effects
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1002/ibd.20131

Background: Infliximab is used for refractory Crohn's disease but there are concerns regarding long‐term safety. Recently, JC‐polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short‐term effect of infliximab on reactivation of several harmful latent viruses. Methods: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein–Barr virus (EBV), human herpes virus‐6, (HHV‐6), ‐7, ‐8, and cytomegalovirus (CMV). Results: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV‐positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV‐PCR tests were transiently positive (>40 copies/105 Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV‐6, ‐7, and ‐8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV‐PCR‐positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Conclusions: Our results support the safety of short‐term infliximab treatment with respect to latent virus reactivation. The long‐term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. (Inflamm Bowel Dis 2007)